Advanced ER-Positive HER2-Negative Breast CancerPhase 2SERENA-2NCT04214288
A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer
A Phase 2 study testing AZD9833 and Fulvestrant in people with Advanced ER-Positive HER2-Negative Breast Cancer, run by AstraZeneca at 85 sites in 16 countries.
Trial summary
This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Advanced ER-Positive HER2-Negative Breast Cancer
- What is being tested?
- AZD9833 and Fulvestrant
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 85 sitesin 16 countries
- Study dates
- 22 Apr 2020to 16 Jun 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Post-menopausal female patients aged at least 18 years.
- Metastatic or loco-regionally recurrent ER-positive HER2-negative adenocarcinoma of the breast.
- Radiological or other objective evidence of progression on or after the last systemic therapy prior to starting study treatment.
- Patients must have at least 1 lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter or in absence of measurable disease as defined above, at least 1 lytic or mixed (lytic+sclerotic) bone lesion.
- Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1.
- Prior endocrine therapy as follows:
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- Recurrence or progression on at least one line of endocrine therapy
- No more than 1 line of endocrine therapy for advanced disease
- No more than 1 line of chemotherapy for advanced disease
- Prior treatment with CDK4/6 inhibitors is permitted
- No prior treatment with fulvestrant, oral selective oestrogen receptor degrader (SERD), or related therapies
- Inclusion criterion for the paired tumour biopsy research subgroup:
- Washout from prior tamoxifen: 4 months to elapse from last tamoxifen dose to pre-dose on-study biopsy.
Who cannot join
- Intervention with any of the following:
- Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
- Use of systemic oestrogen-containing hormone replacement therapy within 6 months prior to the first dose of study treatment.
- Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4/5 and sensitive CYP2B6 substrates, and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index or inability to stop use within the washout period prior to receiving the first dose of study treatment.
- Drugs that are known to prolong QT and have a known risk of torsades de pointes.
- The following cardiovascular criteria: QTcF >470 ms, resting heart rate <45 bpm, clinically significant abnormalities of resting electrocardiogram, uncontrolled hypertension, symptomatic hypotension, factors that increase the risk for QTc prolongation, left ventricular ejection fraction <50%.
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- Radiotherapy with a limited field of radiation for palliation within 1 week of dosing, or to > 30% of bone marrow or a wide field within 4 weeks of dosing.
- Major surgical procedure or significant traumatic injury.
- Presence of life-threatening metastatic visceral disease or uncontrolled central nervous system metastatic disease.
- Inadequate bone marrow reserve or organ function.
- Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833.
- History of hypersensitivity to active or inactive excipients of AZD9833 or fulvestrant.
- Previous randomisation in the present study.
- Women of childbearing potential.
Trial locations and contacts
85 sites in 16 countries.
85 sites in 16 countries
Italy10 sites
Research Site
Bologna, 40138
Research Site
Catanzaro, 88100
Research Site
Meldola, 47014
Research Site
Messina, 98158
Research Site
Milan, 20141
Research Site
Milan, 20121
Research Site
Monza, 20900
Research Site
Naples, 80131
Research Site
Roma, 00128
Research Site
Umbria, 5100
Russia10 sites
Research Site
Kazan', 420029
Research Site
Krasnodar, 350040
Research Site
Kursk, 305035
Research Site
Moscow, 115478
Research Site
Moscow, 123056
Research Site
Pyatigorsk, 357502
Research Site
Ryazan, 390011
Research Site
Saint Petersburg, 197082
Research Site
Saint Petersburg, 197758
Research Site
Volgograd, 400138
United States9 sites
Research Site
Birmingham, Alabama, 35205
Research Site
Canton, Ohio, 44710
Research Site
Chattanooga, Tennessee, 37404
Research Site
Eagle River, Wisconsin, 54521
Research Site
Fort Myers, Florida, 33901
Research Site
Lincoln, Nebraska, 68506
Research Site
Long Beach, California, 90806
Research Site
Nashville, Tennessee, 37203
Research Site
St. Petersburg, Florida, 33705
Belgium7 sites
Research Site
Brasschaat, 2930
Research Site
Charleroi, 6000
Research Site
Ghent, 9000
Research Site
Haine-Saint-Paul, 7100
Research Site
Leuven, 3000
Research Site
Libramont-Chevigny, 6800
Research Site
Namur, 5000
Hungary7 sites
Research Site
Budapest, 1122
Research Site
Debrecen, 4032
Research Site
Kaposvár, 7400
Research Site
Kecskemét, 6000
Research Site
Nyíregyháza, 4400
Research Site
Pécs, 7624
Research Site
Szeged, 6725
Georgia6 sites
Research Site
Batumi, 6000
Research Site
Tbilisi, '0112
Research Site
Tbilisi, '0159
Research Site
Tbilisi, '0186
Research Site
Tbilisi, 0159
Research Site
Tbilisi, 0186
Poland6 sites
Research Site
Bydgoszcz, 85-796
Research Site
Lodz, 93-513
Research Site
Piła, 64-920
Research Site
Rzeszów, 35-021
Research Site
Skorzewo, 60-185
Research Site
Warsaw, 02-781
Ukraine6 sites
Research Site
Cherkasy, 18009
Research Site
Chernivtsі, 58013
Research Site
Kyiv, 03039
Research Site
M. Kyiv, 02094
Research Site
S. Khodosivka, 08173
Research Site
Uzhhorod, 88000
Israel4 sites
Research Site
Jerusalem, 91031
Research Site
Jerusalem, 9112001
Research Site
Nahariya, 22100
Research Site
Petah Tikva, 4941492
Portugal4 sites
Research Site
Almada, 2805-267
Research Site
Lisbon, 1400-038
Research Site
Lisbon, 1449-005
Research Site
Lisbon, 1998-018
Spain4 sites
Research Site
Barcelona, 08190
Research Site
Madrid, 28050
Research Site
Seville, 41013
Research Site
Zaragoza, 50009
Canada3 sites
Research Site
Greenfield Park, Quebec, J4V 2H1
Research Site
Montreal, Quebec, H1T 2M4
Research Site
Montreal, Quebec, H3T 1E2
Germany3 sites
Research Site
Berlin, 10707
Research Site
Düsseldorf, 40225
Research Site
Essen, 45136
France2 sites
Research Site
Paris, 75005
Research Site
Vandœuvre-lès-Nancy, 54519
South Korea2 sites
Research Site
Goyang-si, 10408
Research Site
Incheon, 405-760
United Kingdom2 sites
Research Site
Derby, DE22 3NE
Research Site
Leicester, LE1 5WW
About this study
Official title: SERENA-2: A Randomised, Open-Label, Parallel-Group, Multicentre Phase 2 Study Comparing the Efficacy and Safety of Oral AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer
This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.
Read the detailed description
Post-menopausal women with histologically or cytologically confirmed metastatic or loco-regionally recurrent ER-positive HER2-negative breast cancer before randomization and fulfilling all of the inclusion criteria and none of the exclusion criteria will be included.
After the screening visit and confirmation of eligibility, patients will be randomly assigned in a 1:1:1:1 ratio to receive 1 of the following 4 treatments, consisting of 4-week treatment cycles until disease progression (assessed by the Investigator as defined by Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1):
- AZD9833 (Dose A)
- AZD9833 (Dose B)
- AZD9833 (Dose C)
- Fulvestrant (500 mg) During the treatment period, patients will have scheduled visits until treatment discontinuation. After the end of treatment, patients will attend 2 safety follow-up visits (at the time of treatment discontinuation and 28 days later) and will continue to be followed for survival.
As of December 2020, the Sponsor stopped enrolment to Dose C.
- Being tested
- AZD9833, Fulvestrant
- Keywords
- Open-Label, Parallel-Group, Fulvestrant, ER-Positive HER2-Negative Breast Cancer, Metastatic, AZD9833, Oral SERD, Camizestrant
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9833Drug
Dosage formulation: AZD9833 tablets will be administered orally.
FulvestrantDrug
Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.
| Study group | Role | What they receive |
|---|---|---|
| AZD9833 Dose A | Experimental | The patients will receive AZD9833 (Dose A). Receives: Drug: AZD9833 |
| AZD9833 Dose B | Experimental | The patients will receive AZD9833 (Dose B). Receives: Drug: AZD9833 |
| AZD9833 Dose C | Experimental | The patients will receive AZD9833 (Dose C). Receives: Drug: AZD9833 |
| Fulvestrant 500 mg | Active comparator | The patients will receive Fulvestrant (500 mg). Receives: Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.
Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Measured: From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)
Secondary outcomes (8)
Objective Response Rate (ORR)
ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Adjusted response rate was presented in this analysis.
Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Measured: From screening until disease progression (up to data cut-off of 29 months)
Duration of Response (DoR)
DoR was assessed by the Investigator as defined by RECIST version 1.1. The DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Measured: From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)
Percentage Change in Tumour Size at 16 Weeks
The percentage change in tumour size at 16 weeks was obtained for each patient, based on RECIST measurements taken at baseline and at 16 weeks. Tumour size is the sum of the longest diameters of the target lesions (TLs). Percentage change in the sum of longest TLs diameters at 16 weeks was measured.
Measured: At Week 16
Overall Survival (OS)
The OS was defined as the time from randomisation to death due to any cause.
Measured: From the date of randomisation until death (up to data cut-off of 29 months)
Clinical Benefit Rate at 24 Weeks (CBR24)
Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization.
Adjusted response rate was presented in this analysis.
Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.
Measured: At Week 24
Plasma Concentrations of AZD9833
The plasma concentrations of AZD9833 at steady state were evaluated.
Measured: Cycle 1 Day 15 (pre-dose), Cycle 1 Day 15 (2h), Cycle 1 Day 15 (4h) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)
Percent Change From Baseline in ER and PgR Expression and Ki67 Labelling Index
The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.
Measured: From baseline to Cycle 2 Day 1 (each cycle is 28 days in length)
Changes From Baseline in Health Related Quality of Life (HRQoL)
To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.
Measured: From Day 1 until end of treatment and safety follow up (up to data cut-off of 29 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2020
- Study start22 Apr 2020
- Primary completion30 Aug 2022
- Study completion16 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced ER-Positive HER2-Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04214288
- Sponsor's protocol ID
- D8530C00002
- Other IDs
- 2023-504974-40-00, 2019-003706-27, 2019, 2023
- Acronym
- SERENA-2
- Status last verified
- Aug 2026
- First submitted
- 27 Dec 2019
- Last updated
- 26 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Publications
Oliveira M, Pominchuk D, Nowecki Z, Hamilton E, Kulyaba Y, Andabekov T, Hotko Y, Melkadze T, Nemsadze G, Neven P, Vladimirov V, Zamagni C, Denys H, Forget F, Horvath Z, Nesterova A, Ajimi M, Kirova B, Klinowska T, Lindemann JPO, Lissa D, Mathewson A, Morrow CJ, Traugottova Z, van Zyl R, Arkania E. Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial. Lancet Oncol. 2024 Nov;25(11):1424-1439. doi: 10.1016/S1470-2045(24)00387-5.
PubMed 39481395Hamilton E, Oliveira M, Turner N, Garcia-Corbacho J, Hernando C, Ciruelos EM, Kabos P, Ruiz-Borrego M, Armstrong A, Patel MR, Vaklavas C, Twelves C, Boni V, Incorvati J, Brier T, Gibbons L, Klinowska T, Lindemann JPO, Morrow CJ, Sykes A, Baird RD. A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results. Ann Oncol. 2024 Aug;35(8):707-717. doi: 10.1016/j.annonc.2024.04.012. Epub 2024 May 8.
PubMed 38729567